The long-term objectives of this research group continues to be the investigation of i) neuro(no)trophic factors that support maintenance, growth, function and repair of selected nerve cells, ii) neurite modulating factors that promote (or inhibit) and guide the growth of neuronal axons in development and adult regeneration, and iii) adult rat models that test the competence of neurotrophic and neurite modulating factors to perform in vivo within the context of adult mammalian central and peripheral nervous systems. The underlying expectation -- now widely shared -- is that such factors may ultimately serve as therapeutic tools in degenerative human diseases (e.g. Alzheimer's, Parkinson's, ALS, etc.) and support long-track axonal regeneration after spinal cord or optic nerve lesions, among others. No information is yet available on what trophic and other factors may influence maintenance and repair of corticospinal (CS) motor neurons: the project will address this question by use of both an in vitro model of developing CS cells and an in vivo model of lesioned adult CNS neurons. Another question concerns nerve growth factor (NGF, the prototype for neurotrophic factors), namely the location and identity of NGF producer cells: this project will explore the possible identity between NGF producers and certain subsets of CNS GABAergic neurons. NGF-containing cells have also been found in the hypothalamus and the anterior pituitary, increasing the perception of important links between NGF and thyroid hormones -- and this project will investigate the nature and regulation of hypothalamic and pituitary NGF. Lastly, even when CNS axons are made to regenerate successfully to their innervation territory, the problem remains of what may regulate their distribution there: this project seeks to characterize the newly recognized occurrence of sedimentable NGF in adult brain extracts and the detection of anchored NGF in adult brain sections and to correlate them with pathways and end stations of regenerating cholinergic CNS afferents.